The role of the immune system in diabetes mellitus is complex and not well defined. The overall objectives of this research project are to investigate the actions of insulin in altering specific functions of macrophages, an important cellular component of the immune system. We have previously described 3 murine cell lines of macrophages which possess surface receptors for insulin. In one of these macrophage cultures, insulin was found to inhibit the potential of macrophages to lyse antibody-coated target cells. Most recently we have found that the macrophage cell lines produce large quantities of collagen and appear to also possess high levels of collagenase activity. Studies are in progress to assess the role of ambient glucose, insulin and insulin-like growth factors on collagen production and degradation in the macrophages. Such studies may not only provide a model system for the study of a specific action of insulin on protein metabolism but in addition could establish macrophage functions which are altered in the diabetic state.